Smoking Cessation Drug Research Articles

Cytisine for smoking cessation: A 40-day treatment with an induction period.

Cytisine is a smoking cessation drug now used worldwide. Most of the data available in the literature predict a 25-day treatment, accepted on the basis of previous clinical experience in Eastern Europe. There are few studies on dosing, and only recently some researchers have tried a longer treatment period. This real-world retrospective cross-sectional study analyzed data collected consecutively from 2015 to 2021, in seven smoking cessation centers in north-central Italy. The aim of this study is to evaluate the effectiveness and tolerability of a 40-day cytisine treatment with an induction phase and a slower reduction schedule. Data were collected from a group of 871 patients treated with cysteine, varenicline, and nicotine replacement therapy (NRT). The sample was not randomized. Behavioral support (4-6 sessions, each lasting 20-30 min, plus the evaluation session) was delivered to all patients. Subgroups taking cytisine (n=543 for 40 days), varenicline (n=281 for 12 weeks), and NRT (n=47 for eight weeks) showed biochemically confirmed smoking abstinence at 6 months of 50.5%, 55.9%, and 51.0%, respectively, with a statistically significant difference between cytisine versus varenicline (p<0.01) but not between cytisine versus NRT (p=0.5597). Adverse events were 4.4% with cytisine and 33.3% with varenicline. Behavioral support was an important factor in effectiveness. This study produced preliminary evidence that the 40-day regimen of cytisine, appears to have less effectiveness in comparison to varenicline but the magnitude of the effect is comparable. The results and tolerability seem to be better than in most other studies.

A bupropion modulatory site in the Gloeobacter violaceus ligand-gated ion channel

Bupropion is an atypical antidepressant and smoking cessation drug that causes adverse effects such as insomnia, irritability, and anxiety. Bupropion inhibits dopamine and norepinephrine reuptake transporters and eukaryotic cation-conducting pentameric ligand-gated ion channels, such as nicotinic acetylcholine and serotonin type 3A receptors, at clinically relevant concentrations. Here, we demonstrate that bupropion also inhibits a prokaryotic homolog of pentameric ligand-gated ion channels, the Gloeobacter violaceus ligand-gated ion channel (GLIC). Using the GLIC as a model, we used molecular docking to predict binding sites for bupropion. Bupropion was found to bind to several sites within the transmembrane domain, with the predominant site being localized to the interface between transmembrane segments M1 and M3 of two adjacent subunits. Residues W213, T214, and W217 in the first transmembrane segment, M1, and F267 and I271 in the third transmembrane segment, M3, most frequently reside within a 4 Å distance from bupropion. We then used single amino acid substitutions at these positions and two-electrode voltage-clamp recordings to determine their impact on bupropion inhibitory effects. The substitution T214F alters bupropion potency by shifting the half-maximal inhibitory concentration to a 13-fold higher value compared to wild-type GLIC. Residue T214 is found within a previously identified binding pocket for neurosteroids and lipids in the GLIC. This intersubunit binding pocket is structurally conserved and almost identical to a binding pocket described for neurosteroids in γ-aminobutyric acid type A receptors. Our data thus suggest that the T214 that lines a previously identified lipophilic binding pocket in GLIC and γ-aminobutyric acid type A receptors is also a modulatory site for bupropion interaction with the GLIC.

Efficacy of bupropion and varenicline genetic markers in choosing pharmacological treatment for smoking cessation, and implications for combining drugs: A randomized controlled trial - GENTSMOKING.

Smoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the genetically favorable markers to choose a smoking cessation drug treatment (precision medicine) was superior to using the most effective drug (varenicline) in terms of abstinence rates. Additionally, combination therapy was tested when monotherapy failed. This partially blind, single-center study randomized (1:1) 361 participants into two major groups. In the genetic group (n=184), CYP2B6 rs2279343 (genotype AA) participants started treatment with bupropion, and CHRNA4 rs1044396 (genotype CT or TT) participants started treatment with varenicline; when genetic favorable to both, participants started treatment with bupropion, and when favorable to neither, on both drugs. In the control group (n=177), participants started treatment with varenicline, regardless of genetic markers. Drug treatment lasted 12 weeks. Efficacy endpoints were abstinence rates at Weeks 4, and Weeks 8-12, biochemically validated by carbon monoxide in exhaled air. Participants who did not achieve complete abstinence at Week 4, regardless of group, were given the choice to receive combination therapy. Abstinence rates were 42.9% (95% CI: 36-64) in the control group versus 30.4% (95% CI: 23-37) in the genetic group at Week 4 (p=0.01); and 74% (95% CI: 67-80) versus 52% (95% CI: 49-64) at Week 12 (p<0.001), respectively. The strategy of combining drugs after Week 4 increased abstinence rates in both groups and the significant difference between genetic and control groups was maintained. Results show that using these selected genetic markers was inferior to starting treatment with varenicline (control group), which is currently the most effective smoking cessation drug; moreover, the addition of bupropion in cases of varenicline monotherapy failure improves the efficacy rate until the end of treatment. NCT03362099.

Applicability of machine learning algorithm to predict the therapeutic intervention success in Brazilian smokers.

Smoking cessation is an important public health policy worldwide. However, as far as we know, there is a lack of screening of variables related to the success of therapeutic intervention (STI) in Brazilian smokers by machine learning (ML) algorithms. To address this gap in the literature, we evaluated the ability of eight ML algorithms to correctly predict the STI in Brazilian smokers who were treated at a smoking cessation program in Brazil between 2006 and 2017. The dataset was composed of 12 variables and the efficacies of the algorithms were measured by accuracy, sensitivity, specificity, positive predictive value (PPV) and area under the receiver operating characteristic curve. We plotted a decision tree flowchart and also measured the odds ratio (OR) between each independent variable and the outcome, and the importance of the variable for the best model based on PPV. The mean global values for the metrics described above were, respectively, 0.675±0.028, 0.803±0.078, 0.485±0.146, 0.705±0.035 and 0.680±0.033. Supporting vector machines performed the best algorithm with a PPV of 0.726±0.031. Smoking cessation drug use was the roof of decision tree with OR of 4.42 and importance of variable of 100.00. Increase in the number of relapses also promoted a positive outcome, while higher consumption of cigarettes resulted in the opposite. In summary, the best model predicted 72.6% of positive outcomes correctly. Smoking cessation drug use and higher number of relapses contributed to quit smoking, while higher consumption of cigarettes showed the opposite effect. There are important strategies to reduce the number of smokers and increase STI by increasing services and drug treatment for smokers.

Nicotine Abuse and Neurodegeneration: Novel Pharmacogenetic Targets to Aid Quitting and Reduce the Risk of Dementia.

Nicotine dependence has deleterious neurological impacts. Previous studies found an association between cigarette smoking and accelerating age-related thinning of the brain's cortex and subsequent cognitive decline. Smoking is considered the third most common risk factor for dementia, which prompted the inclusion of smoking cessation in dementia prevention strategies. Traditional pharmacologic options for smoking cessation include nicotine transdermal patches, bupropion and varenicline. However, based on smokers' genetic makeup, pharmacogenetics can be used to develop novel therapies to replace these traditional approaches. Genetic variability of cytochrome P450 2A6 has a major impact on smokers' behavior and their response to quitting therapies. Gene polymorphism in nicotinic acetylcholine receptor subunits also has a great influence on the ability to quit smoking. In addition, polymorphism of certain nicotinic acetylcholine receptors was found to affect the risk of dementia and the impact of tobacco smoking on the development of Alzheimer's disease. Nicotine dependence involves the activation of pleasure response through the stimulation of dopamine release. Central dopamine receptors, catechol-o-methyltransferase and the dopamine transporter protein, regulate synaptic dopamine levels. The genes of these molecules are potential targets for novel smoking cessation drugs. Pharmacogenetic studies of smoking cessation also investigated other molecules, such as ANKK1 and dopamine-beta-hydroxylase (DBH). In this perspective article, we aim to highlight the promising role of pharmacogenetics in the development of effective drugs for smoking cessation, which can increase the success rate of smoking quitting plans and ultimately reduce the incidence of neurodegeneration and dementia.

Antioxidant Activity and Cytotoxicity of Cyanthilium Cinereum and Cinnamon-in Vitro Study

Introduction: Cyanthillium cinereum is a native of tropical Africa and Asia (India, Indochina, Indonesia) and is used as a smoking cessation drug and relief for cold. Leaves act as an abortifacient and blood purifier and have diuretic, antiviral, analgesic, antipyretic, and anti-inflammatory properties. Cinnamon is the inner bark of cinnamon cassia found on the west coast of India, Sri Lanka, and Indonesia. It is a forest evergreen tree that has antioxidant, anti-inflammatory, anti-diabetic, and anti-microbial properties, treats bronchitis, diabetes and has traces of Vitamin B &amp; K. Hence, we aimed to study the antioxidant activity and cytotoxicity in the herbal synergy of cinnamon and cyanthillium cinereum. Materials and Methods: An in vitro study was conducted, and the polar aqueous extract of this combination of herbs cinnamon \ and cyanthilium cinereum was prepared and tested for DPPH assay assay to study its antioxidant properties and the absorbance value was evaluated. Brine Shrimp Assay with viable nauplii cell lines was used for cytotoxicity assessment. Results: Antioxidant activity of the aqueous extract of Cyanthillium cinereum and Cinnamon revealed that there was a decrease in the antioxidant activity with an increase in the concentration of the aqueous extract. Cytotoxicity of the aqueous extract of Cyanthillium cinereum and Cinnamon reported an increase in the cytotoxic activity with a rise in the concentration of the aqueous extract. Conclusion: This research showed that aqueous extract of cinnamon and cyanthillium cinereum has good antioxidant activity, is less cytotoxic, and can be used as a therapeutic and preventive medicine.

Evaluation of an Image-Derived Input Function for Kinetic Modeling of Nicotinic Acetylcholine Receptor-Binding PET Ligands in Mice.

Positron emission tomography (PET) radioligands that bind with high-affinity to α4β2-type nicotinic receptors (α4β2Rs) allow for in vivo investigations of the mechanisms underlying nicotine addiction and smoking cessation. Here, we investigate the use of an image-derived arterial input function and the cerebellum for kinetic analysis of radioligand binding in mice. Two radioligands were explored: 2-[18F]FA85380 (2-FA), displaying similar pKa and binding affinity to the smoking cessation drug varenicline (Chantix), and [18F]Nifene, displaying similar pKa and binding affinity to nicotine. Time-activity curves of the left ventricle of the heart displayed similar distribution across wild type mice, mice lacking the β2-subunit for ligand binding, and acute nicotine-treated mice, whereas reference tissue binding displayed high variation between groups. Binding potential estimated from a two-tissue compartment model fit of the data with the image-derived input function were higher than estimates from reference tissue-based estimations. Rate constants of radioligand dissociation were very slow for 2-FA and very fast for Nifene. We conclude that using an image-derived input function for kinetic modeling of nicotinic PET ligands provides suitable results compared to reference tissue-based methods and that the chemical properties of 2-FA and Nifene are suitable to study receptor response to nicotine addiction and smoking cessation therapies.

Transcranial Magnetic Stimulation as a Tool to Promote Smoking Cessation and Decrease Drug and Alcohol Use.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, drug-free, neural-circuit-based therapeutic tool that was recently cleared by the United States Food and Drug Associate for the treatment of smoking cessation. TMS has been investigated as a tool to reduce consumption and craving for many other substance use disorders (SUDs). This review starts with a discussion of neural networks involved in the addiction process. It then provides a framework for the therapeutic efficacy of TMS describing the role of executive control circuits, default mode, and salience circuits as putative targets for neuromodulation (via targeting the DLPFC, MPFC, cingulate, and insula bilaterally). A series of the largest studies of TMS in SUDs are listed and discussed in the context of this framework. Our review concludes with an assessment of the current state of knowledge regarding the use of rTMS as a therapeutic tool in reducing drug, alcohol, and nicotine use and identifies gaps in the literature that need to be addressed in future studies. Namely, while the presumed mechanism through which TMS exerts its effects is by modulating the functional connectivity circuits involved in executive control and salience of drug-related cues, it is also possible that TMS has direct effects on subcortical dopamine, a hypothesis that could be explored in greater detail with PET imaging.

Research of prospects of involving pharmacists in ukraine to help patients trying to quit smoking

The aim. The study aimed to determine the prevalence of tobacco smoking among pharmacy workers in Ukraine, their awareness of the harmfulness of certain types of cigarettes, the attitude of pharmacy managers and pharmacists towards their colleagues’ smoking, as well as the ability of pharmacists to provide effective help in smoking cessation and assessment of prospects for the participation of pharmacists in tobacco smoking control programs if such programs are to be implemented in Ukraine.&#x0D; Materials and methods. The survey involved 239 employees of Ukrainian pharmacies under the age of 30 working in different regions. According to the geographical structure, the respondents represent 22 regions of Ukraine.&#x0D; Results. The experience of countries where active assistance to those who want to quit smoking pharmacists are involved suggests that pharmacists' support can help increase adherence to smoking cessation drugs and provide additional behavioural support as an adjunct to pharmacotherapy, which is quite effective. Currently, there are no such programs in Ukraine.&#x0D; The survey results show that Ukrainian pharmacists under the age of 30 are aware of the dangers of smoking. Most of them assess the level of their training in smoking cessation assistance as sufficient, but they only mean advice on the use of drugs in smoking cessation.&#x0D; Conclusions. Thus, in order to introduce the services of active support by pharmacists for people trying to quit smoking in Ukraine, it is required to create the necessary conditions for the interest of pharmacies and pharmacists in carrying out this type of activity and the implementation of programs of additional training in methods of active support for people trying to quit smoking

Drug abuse and suicidal thoughts among employees: an emerging economy perspective

PurposeAnchored with turbulence emanating from the COVID-19 pandemic, the work environment has become more stressful with debilitating effects on the well-being of employees. Employees rely on varying means of coping including drug abuse. However, the association between drug abuse and suicidal thoughts among employees in Ghana is unknown. Therefore, this study sought to examine the relationship between drug abuse and suicidal thoughts among employees in Ghana.Design/methodology/approachIn a cross-sectional survey, this study purposively sampled 470 employees from three sectors of the Ghanaian economy (telecommunication, banking and manufacturing). The data was analysed using the multivariate analysis (MANOVA), Pearson’s r test and hierarchical regression.FindingsAnalysis of data revealed a positive relationship between drug abuse and suicidal thoughts, indicating that drug abuse is a risk factor for suicidal thoughts. Besides, it was also revealed that banking sector employees have a higher risk of having suicidal thoughts than employees in the telecommunication and manufacturing sectors.Practical implicationsManagers of organisations need to redesign work to embrace the challenging circumstances brought about as a result of COVID-19 and post-COVID implications. The work environment needs to be more supportive to shield employees from the physical and emotional demands of work during and after this period of the COVID-19 pandemic. Today than ever, investment in the implementation of employee-assisted programmes (EAPs) and employee well-being programmes (EWPs) to equip employees with the needed skills to cope with stressful conditions has been more than justified.Originality/valueFrom a broader perspective, this study identifies drug abuse as a key risk factor for suicidal thoughts among employees, thereby highlighting the fact that smoking cessation programs and drug management therapies are an integral part of well-being programmes aimed at establishing equilibrium and gradually creating a wide gap between employees and suicidal thoughts.

Effectiveness of Health Coaching in Smoking Cessation and Promoting the Use of Oral Smoking Cessation Drugs in Patients with Type 2 Diabetes: A Randomized Controlled Trial

This study looked into the effectiveness of a 6 month health coaching intervention in smoking cessation and smoking reduction for patients with type 2 diabetes. The study was carried out via a two-armed, double-blind, randomized-controlled trial with 68 participants at a medical center in Taiwan. The intervention group received health coaching for 6 months, while the control group only received usual smoking cessation services; some patients in both groups participated in a pharmacotherapy plan. The health coaching intervention is a patient-centered approach to disease management which focuses on changing their actual behaviors. By targeting on achieving effective adult learning cycles, health coaching aims to help patients to establish new behavior patterns and habits. In this study, the intervention group had significantly more participants who reduced their level of cigarette smoking by at least 50% than the control group (p = 0.030). Moreover, patients participating in the pharmacotherapy plan in the coaching intervention group had a significant effect on smoking cessation (p = 0.011), but it was insignificant in the control group. Health coaching can be an effective approach to assisting patients with type 2 diabetes participating in a pharmacotherapy plan to reduce smoking and may help those who participate in pharmacotherapy plan to quit smoking more effectively. Further studies with higher-quality evidence on the effectiveness of health coaching in smoking cessation and the use of oral smoking cessation drugs in patients with type 2 diabetes are needed.

Estudio de correlación entre diferentes escalas que miden la dependencia al tabaquismo

ObjectiveTo analyze the correlation between the degrees of smoking dependence, measured with the Fagerström Test Nicotine Dependence (FTND), Glover-Nilsson Smoking Behavioral Dependence (GN-SBQ) and a measure of self-perceived-dependence (SPD). DesignCross-sectional descriptive observational study. SiteUrban primary health-care center. ParticipantsMen and women between 18 and 65 years old, daily smokers, selected by non-random consecutive sampling. InterventionsSelf-administration of various questionnaires though an electronic device. Main measurementsAge, sex and nicotine dependence assessed by: FTND, GN-SBQ and SPD. Statistical analysis, with SPSS 15.0: descriptive statistics, Pearson correlation analysis and conformity analysis. ResultsTwo hundred fourteen smokers were included, 54.7% were women. Median age 52 years (range: 27-65). Depending on the test used, different results of the high/very high degree of dependence were found: FTND 17.3%, GN-SBQ 15.4% and SPD 69.6%. A moderate magnitude (r≈0.5) correlation between the 3 test was found. When assessing concordance, comparing the FTND with SPD, 70.6% of smokers didn’t coincide in the severity of dependence, reporting a milder degree of dependence with the FTND than with SPD. Comparing GN-SBQ versus FTND, showed conformity in 44.4% of patients while in 40.7%, the FTND underestimated the severity of dependence. Likewise, when comparing SPD with the GN-SBQ, in the 64% GN-SBQ underestimates, while in 34.1% smokers conformity was demonstrated. ConclusionsThe number of patients who consider their SPD to be high/very high was four times higher compared to the GN-SBQ or the FNTD; the latter, being the most demanding, categorizing patients with very high dependence. Requiring a FTND score greater than 7 to prescribe drugs for smoking cessation may exclude subsidiary patients from receiving treatment.

Heat capacity of cytisine – the drug for smoking cessation

The characterization of cytisine (CYT) and its blends with poly(lactic acid) was performed using thermal analysis, elemental analysis, infrared spectroscopy, and powder X-ray diffractometry. The heat capacities, total enthalpy, and phase transitions of CYT were established from 1.8 to 448.15 K (−271.35 – 175 °C) by advanced thermal analysis. Data were obtained using a Quantum Design Physical Property Measurement System (PPMS) and a differential scanning calorimetry (DSC). The low-temperature heat capacity of the crystalline CYT in the range of 1.8 to 300 K (−271.35 – 26.86 °C) was measured by PPMS and fitted to a theoretical model in the low temperature region below 11 K (−262.15 °C), to orthogonal polynomials in the middle range 5 K <T < 60 K (−268.15 °C < t < −213.15 °C) and to the Debye and Einstein functions in the high range of temperature above 60 K (−213.15 °C). The liquid heat capacity was calculated based on the approximated linear regression data above the molten state of the experimental heat capacity of CYT obtained by the standard DSC measurements, and it was expressed as Cpliquid = 0.0838T + 346.78 J·K−1·mol−1. The calculated heat capacity in the solid state was extended to a higher temperature and was used, together with liquid heat capacity, as the reference baselines for the advanced thermal analysis of CYT. The PPMS and DSC/TMDSC methods are complementary methods for thermal analysis of cytisine. The PPMS method allowed determination of the equilibrium heat capacity in the solid state, which together with the equilibrium heat capacity in the liquid state allowed to analyze of the experimental apparent heat capacity of cytisine obtained based on DSC. The melting temperature and the total heat of fusion of crystalline material were established as 431.8 K (158.65 °C) and 26.5 kJ·mol−1, respectively. The solid and liquid heat capacities and transition parameters of CYT were applied to calculate total enthalpies for fully amorphous and crystalline states. Analyses of DSC and X-ray confirmed the presence of the solid-solid transition linking with not so far described a polymorphism phenomenon of CYT. Based on the thermogravimetric analysis the temperature of degradation of CYT was determined as 460.5 K (187.35 °C). Also, a preliminary thermal analysis of the blends of cytisine and poly(lactic acid) as a new candidate for drug delivery system was presented.

Smoking cessation drug led to almost a third of smokers quitting during phase III trial

Smoking cessation drug led to almost a third of smokers quitting during phase III trial

Insights Into the Differential Desensitization of α4β2 Nicotinic Acetylcholine Receptor Isoforms Obtained With Positive Allosteric Modulation of Mutant Receptors.

The development of highly efficacious positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptors (nAChR) has proven useful in defining the ligand dependence of the conformational dynamics of α7 receptors. No such effective modulators are known to exist for the α4β2 nAChR of the brain, limiting our ability to understand the importance of desensitization for the activity profile of specific ligands. In this study, we used mutant β2 subunits that allowed the use of the α7 PAM 3a,4,5,9b-tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS) to probe the desensitizing effects of nicotinic ligands on the two forms of α4β2 receptors; high sensitivity (HS) (two α4 and three β2 subunits) and low sensitivity (LS) (three α4 and two β2 subunits). A total of 28 different ligands of 8 different categories, based on activity and selectivity, were tested for their ability to induce TQS-sensitive desensitization of HS and LS α4β2 receptors. Results confirm that HS α4β2 receptor responses are strongly limited by desensitization, by at least an order of magnitude more so than the responses of LS receptors. The activation of α4β2 receptors by the smoking-cessation drugs cytisine and varenicline is strongly limited by desensitization, as is the activation of LS receptors by the HS-selective agonists 6-[5-[(2S)-2-Azetidinylmethoxy]-3-pyridinyl]-5-hexyn-1-ol dihydrochloride and 4-(5-ethoxy-3-pyridinyl)-N-methyl-(3E)-3-buten-1-amine difumarate. The evaluation of drugs previously identified as α7-selective agonists revealed varying patterns of α4β2 cross-desensitization that were predictive of the effects of these drugs on the activation of wild-type α4β2 receptors by acetylcholine, supporting the utility of TQS-sensitive receptors for the development of focused therapeutics. SIGNIFICANCE STATEMENT: To varying degrees, ligands regulate the balance of active and desensitized states of the two forms of the primary nAChR subtypes in brain. Using mutant beta subunits, an allosteric modulator can reverse ligand-induced desensitization, revealing the differential desensitization of the receptors by specific ligands. This study shows that drugs believed to be selective for therapeutic targets may cross-desensitize other targets and that, within a class of drugs, improved specificity can be achieved by using agents that reduce such cross-desensitization.

Effect of in-hospital nurse-led smoking cessation intervention for patients with atherosclerotic cardiovascular disease: a randomised pilot study

Abstract Background Smoking remains prevalent after cardiovascular disease (CVD) events and knowledge on how to facilitate effective cessation in clinical practice is needed. Purpose To test the effect of an in-hospital nurse-led intervention on the participation rate at municipal Healthy Life Centres (HLC) and the use of smoking cessation drugs. Secondary, to determine long-term effects on cessation rates. Methods A prospective, randomized, open-label, parallel-group intervention pilot-study was conducted at a Norwegian secondary care hospital in 2021. Patients with atherosclerotic CVD who smoked at least one cigarette daily when admitted with an acute CVD event were consecutively included. The nurse-led intervention included cessation counselling utilizing motivational interview technique, information and guidance in proper use of cessation drugs and direct referral to a 12-weeks digital (video ± phone) HLC program where patients received free cessation drugs. The low-threshold intervention included written information about the offer in the HLC with free cessation drugs. The primary endpoints were between-group differences in attendance rates at the HLC program and the use of cessation drugs. Results Of 99 potential participants, 24 did not meet the entry criteria whereas 17 declined to participate. Of 58 randomised patients, three died during follow-up and 55 completed the study. Mean age was 65.7 (SD 9.2) years, 35% were female, 88% had low education, 88% had smoked &amp;gt;20 years, and motivation for quitting smoking was high (mean 8.5 on a 0 [no motivation] to 10 [high motivation] Likert scale). Comorbidity was common (mean Charlson score 5.1) and 40% had symptoms of anxiety and/or depression. The nurse-led intervention resulted in significantly higher participation rate at the HLC (48% vs. 4%, difference: 44% [95% CI: 24%, 65%], P&amp;lt;0.0001) and more frequent use of cessation drugs (48% vs. 11%, difference: 37% [95% CI: 15%, 60%], P=0.002) compared to the low-threshold intervention (Figure A). All participants in the intervention group who attended the HLC program were offered follow-up within 21 days following randomisation. In the intervention group 15% used varenicline and 33% used a combination of short and long-acting nicotine replacements. Clinically significant differences in cessation rates after six months were observed between the groups (Figure B). Concomitant carbon monoxide measurements were obtained of 5 participants in the intervention group and 4 in the control group who reported cessation and all confirmed non-smoking. Conclusion Among multi-morbid patients hospitalised for a CVD event, a nurse-led intervention resulted in substantially higher participation rate at a municipal HLC program and higher use of smoking cessation drugs compared to written information. We also found clinically significant long-term effects on cessation rates which needs to be confirmed in a large-scale study. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Dam Foundation

Shared Decision-Making in Drug Selection for Improving Effectiveness of Smoking Cessation

&lt;p&gt;目的：探討使用決策輔助工具(patient decision aids, PDA)選擇戒菸藥物，是否能提升戒菸成效。&lt;/p&gt; &lt;p&gt;方法：本研究是一篇歷史對照研究(historical control trial)，研發一份紙本決策輔助工具，輔助戒菸者在varenicline與合併尼古丁替代療法(combination nicotine replacement therapy)兩類藥物中做出選擇。2020年1月至2021年3月期間，於家庭醫學科戒菸門診進行收案，針對有意願接受藥物戒菸的民眾，由醫師擔任醫病共享決策的引導員(coach)，使用決策輔助工具協助其決定藥物的種類。對照組為2019年全年度在家庭醫學科戒菸門診接受藥物戒菸服務者，無使用決策輔助工具。以電話訪問調查第三個月以及第六個月的戒菸狀況，再以logistic regression等統計方法探討使用PDA是否影響戒菸成功率。&lt;/p&gt; &lt;p&gt;結果：排除療程中更換處方和失聯者，總共199人被納入研究（PDA組62人：男性佔80.6%，平均年齡為46.0歲；對照組137人，男性佔74.5%，平均年齡為49.4歲）。PDA組傾向選擇varenicline作為戒菸藥物(aOR=1.94, 95% CI 1.02-3.71)；兩組六個月點戒菸率無顯著差異(aOR=1.43, 95% CI 0.74-2.79)。&lt;/p&gt; &lt;p&gt;結論：以決策輔助工具選擇戒菸藥物，民眾偏好varenicline甚於合併尼古丁替代療法，但是並未對戒菸成功率造成顯著影響。醫病共享決策能否提升戒菸藥物的順從性，並增進戒菸治療的效益，需要進一步的研究。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Purpose: The study explored whether the use of patient decision aid (PDA) to select smoking cessation drugs can improve the effectiveness of smoking cessation.&lt;/p&gt; &lt;p&gt;Methods: This historical control trail developed a paper-based PDA to help smokers choose between varenicline and a combination of nicotine replacement therapy. From January 2020 to March 2021, people visiting the smoking cessation clinic of a family medicine department and willing to take drugs to quit smoking were enrolled into the PDA group of the study with doctors serving as coaches for shared decision-making and applying the PDA to help them decide on the types of drugs to use. Members in the control group were enrolled from people receiving the drug smoking cessation services in the same smoking cessation clinic in 2019 without using PDA. The smoking status after 3 and 6 months were collected by telephone interview. The effects of using PDA on smoking cessation were analyzed by logistic regression.&lt;/p&gt; &lt;p&gt;Results: A total of 199 people participating in the study, excluding those who changed prescriptions and lost contact during the course of treatment. Of the 62 participants in the PDA group, 80.6% were male, and the average age was 46.0. Of the 137 participants in the control group, 74.5% were male, and the average age was 49.4. The PDA group preferred varenicline as the smoking cessation drug (aOR=1.94, 95% CI 1.02-3.71). There was no significant difference in the smoking cessation rate between the two groups at six months (aOR=1.43, 95% CI 0.74-2.79).&lt;/p&gt; &lt;p&gt;Conclusion: When using PDA to select smoking cessation drugs, people appear to prefer varenicline over a combination of nicotine replacement therapy; however, this preference produces no significant influence on the success rate of smoking cessation. Whether shared decision-making help improve the compliance with the instructions of smoking cessation products and enhance the effectiveness of smoking cessation treatment requires further research.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Characterization of Binding Site Interactions and Selectivity Principles in the α3β4 Nicotinic Acetylcholine Receptor.

Nicotinic acetylcholine receptors (nAChRs) play an important role in neurotransmission and are also involved in addiction and several disease states. There is significant interest in therapeutic targeting of nAChRs; however, achieving selectivity for one subtype over others has been a longstanding challenge, given the close structural similarities across the family. Here, we characterize binding interactions in the α3β4 nAChR subtype via structure-function studies involving noncanonical amino acid mutagenesis and two-electrode voltage clamp electrophysiology. We establish comprehensive binding models for both the endogenous neurotransmitter ACh and the smoking cessation drug cytisine. We also use a panel of C(10)-substituted cytisine derivatives to probe the effects of subtle changes in the ligand structure on binding. By comparing our results to those obtained for the well-studied α4β2 subtype, we identify several features of both the receptor and agonist structure that can be utilized to enhance selectivity for either α3β4 or α4β2. Finally, we characterize binding interactions of the α3β4-selective partial agonist AT-1001 to determine factors that contribute to its selectivity. These results shed new light on the design of selective nAChR-targeted ligands and can be used to inform the design of improved therapies with minimized off-target effects.

Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Type 2 Diabetes

Evidence of effective smoking cessation interventions in patients with diabetes is limited. The unique behavioral and metabolic characteristics of smokers with type 2 diabetes warrants a randomized clinical trial of the smoking cessation drug varenicline. To evaluate the efficacy and safety of varenicline in patients with type 2 diabetes with an intention to quit smoking. This multicenter, double-blind, placebo-controlled randomized clinical trial recruited patients from 6 outpatient clinics in 5 hospitals in Catania, Italy. Patients with type 2 diabetes, who were smoking at least 10 cigarettes a day, and who intended to quit smoking were screened for eligibility. Eligible patients were randomized to either varenicline or placebo treatment. The trial consisted of a 12-week treatment phase followed by a 40-week follow-up, nontreatment phase. Intention-to-treat data analysis was performed from December 2020 to April 2021. Varenicline, 1 mg, twice daily or matched placebo administered for 12 weeks. Patients in both treatment groups also received smoking cessation counseling. The primary efficacy end point of the study was the continuous abstinence rate (CAR) at weeks 9 to 24. Secondary efficacy end points were the CAR at weeks 9 to 12 and weeks 9 to 52 as well as 7-day point prevalence of abstinence at weeks 12, 24, and 52. A total of 300 patients (mean [SD] age, 57.4 [0.8] years; 117 men [78.0%] in varenicline group and 119 men [79.3%] in placebo group) were randomized to receive varenicline (n = 150) or placebo (n = 150). The CAR at weeks 9 to 24 was significantly higher for the varenicline than placebo group (24.0% vs 6.0%; odds ratio [OR], 4.95; 95% CI, 2.29-10.70; P < .001). The CARs at weeks 9 to 12 (31.3% vs 7.3%; OR, 5.77; 95% CI, 2.85-11.66; P < .001) and weeks 9 to 52 (18.7% vs 5.3%; OR, 4.07; 95% CI, 1.79-9.27; P < .001) as well as the 7-day point prevalence of abstinence at weeks 12, 24, and 52 were also significantly higher for the varenicline vs placebo group. The most frequent adverse events occurring in the varenicline group compared with the placebo group were nausea (41 [27.3%] vs 17 [11.4%]), insomnia (29 [19.4%] vs 19 [12.7%]), abnormal dreams (19 [12.7%] vs 5 [3.4%]), anxiety (17 [11.4%] vs 11 [7.3%]), and irritability (14 [9.4%] vs 8 [5.4%]). Serious adverse events were infrequent in both groups and not treatment-related. Results of this trial showed that inclusion of varenicline in a smoking cessation program is efficacious in achieving long-term abstinence without serious adverse events. Varenicline should be routinely used in diabetes education programs to help patients with type 2 diabetes stop smoking. ClinicalTrials.gov Identifier: NCT01387425.

Effect evaluation of "Smoking cessation: Doctor first"program in China

Objective: To evaluate the effect of "Smoking cessation: Doctor first" program on smoking medical staff. Methods: From December 2016 to September 2019, 1 747 smoking medical staff from 54 units of China Tobacco Cessation Alliance were enrolled into"Smoking cessation: Doctor first"program. Demographic characteristics, smoking characteristics, degree of tobacco dependence, willingness to quit smoking and other related factors were collected during the baseline survey. Multivariate logistic regression model was used to analyze the related factors of willingness to quit. The subjects were given intensive smoking cessation intervention from October 2017 to September 2019, including education on the hazards of smoking, methods of smoking cessation and giving smoking cessation drugs. After intervention, the subjects were investigated about their smoking cessation progress and the effect of the project was evaluated. Results: The subjects were (41±11) years old, 91.9% (1 609/1 747) were male and 62.2% (1 086/1 747) were daily smokers. The main reasons for smoking included the influence of friends [697 (39.9%)], the need for social entertainment [629 (36.0%)], the relief of mental stress [589 (33.7%)] and the refreshment [459 (26.3%)]. At baseline, 52.9% (885/1 672) and 43.2% (755/1 747) smokers had intention to quit smoking and had planned to quit within one year, respectively. Multivariate logistic regression model analysis showed that: low education level [OR (95%CI) of high school and junior high school and below were 2.42 (1.61, 3.63) and 1.57 (1.18, 2.11)], daily smoking [OR (95%CI): 1.38 (1.06, 1.78)], thinking quitting smoking is not important [OR (95%CI): 4.15 (3.33, 5.18)] and having no quitting experience [OR (95%CI): 3.21 (2.53, 4.05)] were associated with no intention to quit smoking. After intensive smoking cessation intervention, 81.0% (1 415/1 747) smokers started to quit and 36.6% (518/1 415) quit smoking with drugs, both higher than the baseline level (all P values<0.001). By the end of the program, 60.2% (852/1 415) of the medical staff had quit smoking successfully. Conclusion: "Smoking cessation: Doctor first"program can improve the willingness to quit and the proportion of using smoking cessation drugs of medical staff.